RESUMO
2-Mercaptoethanesulfonate (mesna) is a nontoxic drug which upon intravenous and oral administration effectively prevents urothelial toxicity in cancer patients treated with oxazaphosphorines. Mesna is rapidly oxidized to dimesna in the blood. It is then taken up by kidney tubular cells in which it is reduced and excreted into the urine as mesna where it reacts with toxic metabolites. We have observed that mesna, but not dimesna, may inhibit growth of several human malignant cell lines in vitro. Some are extremely sensitive, whereas others are more or less resistant. It was found that 2/4 relatively resistant human bladder cancer cell lines turned sensitive upon repeated administrations of mesna and 5/5 cell lines appeared to be sensitive to mesna when grown in serum-free medium. The results seem to provide an explanation of the remarkable positive clinical effects of prolonged oral mesna treatment in patients with superficial bladder cancer.
Assuntos
Replicação do DNA/efeitos dos fármacos , Mesna/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Cinética , Mesna/uso terapêutico , Proteínas de Neoplasias/biossíntese , Prolina/metabolismo , RNA Neoplásico/biossíntese , RNA Neoplásico/efeitos dos fármacos , Timidina/metabolismo , Uridina/metabolismoRESUMO
2-Mercaptoethanesulfonate (mesna), which is used as an uroprotector during oxazaphosphorine therapy of cancer patients, was found to inhibit growth of several cultured human malignant cell lines in vitro. Dimesna, which is rapidly formed in the blood of mesna treated patients, had no effect and did not interfere with the growth inhibitory activity of mesna. For sensitive cell lines, complete growth inhibitions were usually observed at mesna concentrations of 10(-4) M. Higher concentrations were less toxic or even stimulated proliferation of some cell lines. There was no experimental evidence that the biphasic dose-response profiles were due to a more complete dimesna formation at high mesna concentrations. Since mesna, which is excreted in its monomeric form in urine, was reported to inhibit growth of superficial bladder cancer in patients, we examined the effects of repeated mesna administrations in cultures of bladder cancer cells. The results showed that this treatment caused growth inhibition of 2/4 "resistant" cell lines. The mechanisms by which mesna inhibits cell growth are unknown and it is not known if it acts selectively on malignant cells.